tbuckley/cabot-search huggingface dataset:
Rural-Urban Disparities in Diagnosis of Early-Onset Dementia
Authors: Wendy Y. Xu, Jeah Jung, Sheldon M. Retchin, Yiting Li, Soumyadipta Roy
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Limited access to appropriate specialists and testing may be associated with delayed diagnosis and symptom management for patients with early-onset Alzheimer disease and related dementias (ADRDs). <h3>Objectives</h3> To examine rural vs urban differences in diagnostic and symptom management service use among patients with early-onset ADRDs. <h3>Design, Setting, and Participants</h3> This cross-sectional study was conducted using commercial claims from 2012 to 2017. Included patients were those with early-onset ADRDs aged 40 to 64 years, including new patients, defined as those with no claims of ADRDs for 36 months before the first ADRD diagnosis. The likelihood of receiving diagnostic and symptom management services was estimated, with adjustment for individual-level variables associated with health care use. Data were analyzed from February 2021 to March 2022. <h3>Exposures</h3> Rural residence. <h3>Main Outcomes and Measures</h3> Among patients with new, early-onset ADRDs, use of psychological assessment and neuropsychological testing performed at the initial diagnosis (index date) or 90 days or less after the index date and use of brain imaging during the 180 days before the index date were collected. Access to different clinicians on the index date or 90 days or less after the index date was also collected, including visits to primary care physicians and nurse practitioners (PCPs) and specialty visits to psychologists, neurologists, and psychiatrists. <h3>Results</h3> Among 71 799 patients with early-onset ADRD (mean [SD] age, 56.34 [6.05] years; 39 231 women [54.64%]), 8430 individuals had new early-onset ADRDs (mean [SD] age, 55.94 [6.30] years; 16 512 women [56.65%]). There were no statistically significant differences between new patients with early-onset ADRDs in rural vs urban areas in the use of psychological assessments, imaging studies, or visits to neurologists or psychiatrists. However, new patients in rural areas were less likely to receive neuropsychological testing (odds ratio [OR], 0.83; 95% CI, 0.70-0.98) or visit a psychologist (OR, 0.72; 95% CI, 0.60-0.85) compared with patients in urban areas. However, new patients in rural areas with early-onset ADRDs were more likely to have only PCP visits for diagnosis and symptom management compared with those in urban areas (OR, 1.40; 95% CI, 1.19-1.66). <h3>Conclusions and Relevance</h3> This study found that new patients with early-onset ADRDs in rural areas were less likely to receive neuropsychological testing or visit psychologists but more likely to be diagnosed and treated exclusively by PCPs compared with those in urban areas. These findings suggest that efforts, such as clinician education or teleconsultative guidance to PCPs, may be needed to enhance access to specialist services in rural areas.
MAPK-interacting kinase 1 regulates platelet production, activation, and thrombosis
Authors: Bhanu Kanth Manne, Robert A. Campbell, Seema Bhatlekar, Abigail Ajanel, Frederik Denorme, Irina Portier, Elizabeth A. Middleton, Neal D. Tolley, Yasuhiro Kosaka, Emilie Montenont, Li Guo, Jesse W. Rowley, Paul F. Bray, Shancy Jacob, Rikiro Fukanaga, Christopher Proud, Andrew S. Weyrich, Matthew T. Rondina
Journal: Blood (2022)
Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene
Authors: Samar Yahya, Claire E.L. Smith, James A. Poulter, Martin McKibbin, Gavin Arno, Jamie Ellingford, Kati Kämpjärvi, Muhammad I. Khan, Frans P.M. Cremers, Alison J. Hardcastle, Bruce Castle, David H.W. Steel, Andrew R. Webster, Graeme C. Black, Mohammed E. El-Asrag, Manir Ali, Carmel Toomes, Chris F. Inglehearn, Stuart Ingram, Rachel Taylor, Forbes Manson, Panagiotis Sergouniotis, Nikolas Pontikos, Michael Cheetham, Alessia Fiorentino, Susan Downes, Jing Yu, Stephanie Halford, Suzanne Broadgate, Veronica van Heyningen, John C. Ambrose, Prabhu Arumugam, Roel Bevers, Marta Bleda, Freya Boardman-Pretty, Christopher R. Boustred, Helen Brittain, Mark J. Caulfield, Georgia C. Chan, Greg Elgar, Tom Fowler, Adam Giess, Angela Hamblin, Shirley Henderson, Tim J.P. Hubbard, Rob Jackson, Louise J. Jones, Dalia Kasperaviciute, Melis Kayikci, Athanasios Kousathanas, Lea Lahnstein, Sarah E.A. Leigh, Ivonne U.S. Leong, Javier F. Lopez, Fiona Maleady-Crowe, Meriel McEntagart, Federico Minneci, Loukas Moutsianas, Michael Mueller, Nirupa Murugaesu, Anna C. Need, Peter O’Donovan, Chris A. Odhams, Christine Patch, Mariana Buongermino Pereira, Daniel Perez-Gil, John Pullinger, Tahrima Rahim, Augusto Rendon, Tim Rogers, Kevin Savage, Kushmita Sawant, Richard H. Scott, Afshan Siddiq, Alexander Sieghart, Samuel C. Smith, Alona Sosinsky, Alexander Stuckey, Mélanie Tanguy, Ana Lisa Taylor Tavares, Ellen R.A. Thomas, Simon R. Thompson, Arianna Tucci, Matthew J. Welland, Eleanor Williams, Katarzyna Witkowska, Suzanne M. Wood
Journal: Ophthalmology (2022)
Prebiotic galactooligosaccharides interact with mouse gut microbiota to attenuate acute graft-versus-host disease
Authors: Zachary C. Holmes, Helen Tang, Congxiao Liu, Amy Bush, Benjamin C. Neubert, Yiqun Jiao, Megan Covington, Diana M. Cardona, Michelle C. Kirtley, Benny J. Chen, Nelson J. Chao, Lawrence A. David, Anthony D. Sung
Journal: Blood (2022)

Previous studies suggest that gut microbiome disruption induced by chemotherapy, dietary deficiencies, and/or antibiotics are associated with increased incidence of acute graft-versus-host disease (aGVHD) following hematopoietic stem cell transplantation (HSCT). In a murine model of antibiotic-induced gut microbiome disruption, Holmes and colleagues show that oral administration of galactooligosaccharides (GOS) as a prebiotic attenuates lethal aGVHD, highlighting the crosstalk between diet and gut microbiota. Their data encourage clinical trials of GOS prebiotic diets during HSCT.
Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
Authors: Laura Videla, Bessy Benejam, Jordi Pegueroles, María Carmona-Iragui, Concepción Padilla, Susana Fernández, Isabel Barroeta, Miren Altuna, Silvia Valldeneu, Diana Garzón, Laia Ribas, Víctor Montal, Javier Arranz Martínez, Mateus Rozalem Aranha, Daniel Alcolea, Alexandre Bejanin, Maria Florencia Iulita, Sebastià Videla Cés, Rafael Blesa, Alberto Lleó, Juan Fortea
Journal: JAMA Network Open (2022)

Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established.To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments.This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia.Neurological and neuropsychological assessments.The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test.A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline.This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.
Functional immunity against SARS-CoV-2 in the general population after a booster campaign and the Delta and Omicron waves, Switzerland, March 2022
Authors: Rebecca Amati, Anja Frei, Marco Kaufmann, Serena Sabatini, Céline Pellaton, Jan Fehr, Emiliano Albanese, Milo A Puhan
Journal: Eurosurveillance (2022)

Functional immunity (defined here as serum neutralising capacity) critically contributes to conferring protection against SARS-CoV-2 infection and severe COVID-19. This cross-sectional analysis of a prospective, population-based cohort study included 1,894 randomly-selected 16 to 99-year-old participants from two Swiss cantons in March 2022. Of these, 97.6% (95% CI: 96.8-98.2%) had anti-spike IgG antibodies, and neutralising capacity was respectively observed for 94%, 92% and 88% against wild-type SARS-CoV-2, Delta and Omicron variants. Studying functional immunity to inform and monitor vaccination campaigns is crucial.
Hepatocellular Carcinoma Incidence in Alcohol-Associated Cirrhosis: Systematic Review and Meta-analysis
Authors: Daniel Q. Huang, Darren J.H. Tan, Cheng Han Ng, Maral Amangurbanova, Nancy Sutter, Phoebe Wen Lin Tay, Wen Hui Lim, Jie Ning Yong, Ansel Tang, Nicholas Syn, Mark D. Muthiah, Eunice X.X. Tan, Shravan Dave, Benjamin Tay, Abdul M. Majzoub, Danielle Gerberi, Beom Kyung Kim, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2022)
Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia–reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination
Authors: Saiyang Xie, Yun Xing, Wenke Shi, Min Zhang, Mengya Chen, Wenxi Fang, Shiqiang Liu, Tong Zhang, Xiaofeng Zeng, Si Chen, Shasha Wang, Wei Deng, Qizhu Tang
Journal: Acta Pharmaceutica Sinica B (2022)

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia-reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia-reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGFβ1-Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10 (USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination, which provided a potential strategy for myocardial IRI and cardiac remodeling.
Signalling and responding to zoonotic threats using a One Health approach: a decade of the Zoonoses Structure in the Netherlands, 2011 to 2021
Authors: Joke van der Giessen, Frits Vlaanderen, Titia Kortbeek, Corien Swaan, Hans van den Kerkhof, Els Broens, Jolianne Rijks, Miriam Koene, Mauro De Rosa, Mathilde Uiterwijk, Marieke Augustijn-Schretlen, Catharina Maassen
Journal: Eurosurveillance (2022)

In the Netherlands, the avian influenza outbreak in poultry in 2003 and the Q fever outbreak in dairy goats between 2007 and 2010 had severe consequences for public health. These outbreaks led to the establishment of an integrated human-veterinary risk analysis system for zoonoses, the Zoonoses Structure. The aim of the Zoonoses Structure is to signal, assess and control emerging zoonoses that may pose a risk to animal and/or human health in an integrated One Health approach. The Signalling Forum Zoonoses (SO-Z), the first step of the Zoonoses Structure, is a multidisciplinary committee composed of experts from the medical, veterinary, entomology and wildlife domains. The SO-Z shares relevant signals with professionals and has monthly meetings. Over the past 10 years (June 2011 to December 2021), 390 different signals of various zoonotic pathogens in animal reservoirs and humans have been assessed. Here, we describe the Zoonoses Structure with examples from signals and responses for four zoonotic events in the Netherlands (tularaemia, Brucella canis , West Nile virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)). This may serve as an example for other countries on how to collaborate in a One Health approach to signal and control emerging zoonoses.
Sindbis virus outbreak and evidence for geographical expansion in Finland, 2021
Authors: Maija T Suvanto, Ruut Uusitalo, Eveline Otte im Kampe, Tytti Vuorinen, Satu Kurkela, Olli Vapalahti, Timothée Dub, Eili Huhtamo, Essi M Korhonen
Journal: Eurosurveillance (2022)

Sindbis virus (SINV) caused a large outbreak in Finland in 2021 with 566 laboratory-confirmed human cases and a notable geographical expansion. Compared with the last large outbreak in 2002, incidence was higher in several hospital districts but lower in traditionally endemic locations in eastern parts of the country. A high incidence is also expected in 2022. Awareness of SINV should be raised in Finland to increase recognition of the disease and prevent transmission through the promotion of control measures.
The role of hypoxia and inflammation in the regulation of iron metabolism and erythropoiesis in COVID‐19: The IRONCOVID study
Authors: Diletta Maira, Lorena Duca, Fabiana Busti, Dario Consonni, Michela Salvatici, Alice Vianello, Angelo Milani, Amedeo Guzzardella, Elena Di Pierro, Stefano Aliberti, Itala Marina Baldini, Alessandra Bandera, Francesco Blasi, Elena Cassinerio, Matteo Cesari, Anna Ludovica Fracanzani, Giacomo Grasselli, Giovanna Graziadei, Rosa Lombardi, Giacomo Marchi, Nicola Montano, Valter Monzani, Flora Peyvandi, Marco Proietti, Maria Sandri, Luca Valenti, Maria Domenica Cappellini, Domenico Girelli, Alessandro Protti, Irene Motta
Journal: American Journal of Hematology (2022)

Coronavirus Disease (COVID-19) can be considered as a human pathological model of inflammation combined with hypoxia. In this setting, both erythropoiesis and iron metabolism appear to be profoundly affected by inflammatory and hypoxic stimuli, which act in the opposite direction on hepcidin regulation. The impact of low blood oxygen levels on erythropoiesis and iron metabolism in the context of human hypoxic disease (e.g., pneumonia) has not been fully elucidated. This multicentric observational study was aimed at investigating the prevalence of anemia, the alterations of iron homeostasis, and the relationship between inflammation, hypoxia, and erythropoietic parameters in a cohort of 481 COVID-19 patients admitted both to medical wards and intensive care units (ICU). Data were collected on admission and after 7 days of hospitalization. On admission, nearly half of the patients were anemic, displaying mild-to-moderate anemia. We found that hepcidin levels were increased during the whole period of observation. The patients with a higher burden of disease (i.e., those who needed intensive care treatment or had a more severe degree of hypoxia) showed lower hepcidin levels, despite having a more marked inflammatory pattern. Erythropoietin (EPO) levels were also lower in the ICU group on admission. After 7 days, EPO levels rose in the ICU group while they remained stable in the non-ICU group, reflecting that the initial hypoxic stimulus was stronger in the first group. These findings strengthen the hypothesis that, at least in the early phases, hypoxia-driven stimuli prevail over inflammation in the regulation of hepcidin and, finally, of erythropoiesis.
Examination of SARS-CoV-2 In-Class Transmission at a Large Urban University With Public Health Mandates Using Epidemiological and Genomic Methodology
Authors: Kayla Kuhfeldt, Jacquelyn Turcinovic, Madison Sullivan, Lena Landaverde, Lynn Doucette-Stamm, Davidson H. Hamer, Judy T. Platt, Catherine Klapperich, Hannah E. Landsberg, John H. Connor
Journal: JAMA Network Open (2022)

<h3>Importance</h3> SARS-CoV-2, the causative agent of COVID-19, has displayed person-to-person transmission in a variety of indoor situations. This potential for robust transmission has posed significant challenges and concerns for day-to-day activities of colleges and universities where indoor learning is a focus for students, faculty, and staff. <h3>Objective</h3> To assess whether in-class instruction without any physical distancing, but with other public health mitigation strategies, is a risk for driving SARS-CoV-2 transmission. <h3>Design, Setting, and Participants</h3> This cohort study examined the evidence for SARS-CoV-2 transmission on a large urban US university campus using contact tracing, class attendance, and whole genome sequencing during the 2021 fall semester. Eligible participants were on-campus and off-campus individuals involved in campus activities. Data were analyzed between September and December 2021. <h3>Exposures</h3> Participation in class and work activities on a campus with mandated vaccination and indoor masking but that was otherwise fully open without physical distancing during a time of ongoing transmission of SARS-CoV-2, both at the university and in the surrounding counties. <h3>Main Outcomes and Measures</h3> Likelihood of in-class infection was assessed by measuring the genetic distance between all potential in-class transmission pairings using polymerase chain reaction testing. <h3>Results</h3> More than 600 000 polymerase chain reaction tests were conducted throughout the semester, with 896 tests (0.1%) showing detectable SARS-CoV-2; there were over 850 cases of SARS-CoV-2 infection identified through weekly surveillance testing of all students and faculty on campus during the fall 2021 semester. The rolling mean average of positive tests ranged between 4 and 27 daily cases. Of more than 140 000 in-person class events and a total student population of 33 000 between graduate and undergraduate students, only 9 instances of potential in-class transmission were identified, accounting for 0.0045% of all classroom meetings. <h3>Conclusions and Relevance</h3> In this cohort study, the data suggested that under robust transmission abatement strategies, in-class instruction was not an appreciable source of disease transmission.
A Multicenter, Prospective, Randomized, <scp>Parallel‐Group</scp> Trial on the Effects of Temporary Methotrexate Discontinuation for One Week Versus Two Weeks on Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis
Authors: Jin Kyun Park, Yun Jong Lee, Kichul Shin, Eun Ha Kang, You‐Jung Ha, Jun Won Park, Min Jung Kim, Mi Hyeon Kim, Se Rim Choi, Youjin Jung, Ju Ho Lee, Ji In Jung, Ju Yeon Kim, Kevin L. Winthrop, Eun Bong Lee
Journal: Arthritis & Rheumatology (2022)

Objective This clinical trial was conducted to investigate whether discontinuing methotrexate (MTX) for 1 week after seasonal influenza vaccination is noninferior to discontinuing for 2 weeks after vaccination in patients with rheumatoid arthritis (RA). Methods In this multicenter, prospective, randomized, parallel‐group noninferiority trial, RA patients receiving a stable dose of MTX were randomly assigned at a ratio of 1:1 to discontinue MTX for 1 week or for 2 weeks after they received the quadrivalent 2021–2022 seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains. The primary outcome measure was the proportion of patients with a satisfactory vaccine response, which was defined as ≥4‐fold increase in antibody titers, as determined with the hemagglutination inhibition assay, against ≥2 of the 4 vaccine strains at 4 weeks after vaccination. Results The modified intent‐to‐treat population included 90 patients in the 1‐week MTX hold group and 88 patients in the 2‐week MTX hold group. The mean ± SD MTX doses were 12.6 ± 3.4 mg/week in the 1‐week MTX hold group and 12.9 ± 3.3 mg/week in the 2‐week MTX hold group. The proportion of satisfactory vaccine responses did not differ between the groups (68.9% versus 75.0%; P = 0.364). The rate of seroprotection and the fold increase in antibody titers for each of the 4 influenza antigens were similar between the groups. Conclusion A temporary discontinuation of MTX for 1 week after vaccination was noninferior to a discontinuation of MTX for 2 weeks after vaccination, regarding induction of a satisfactory vaccine response to a seasonal influenza vaccine in patients with RA receiving a stable dose of MTX. image
Management of an esophagopleural fistula after resection of giant submucosal tumor of the cardia
Authors: Zu-Qiang Liu, Li Wang, Jing-Zheng Liu, Zhi-Peng Qi, Quan-Lin Li, Ping-Hong Zhou
Journal: Endoscopy (2022)

A 24-year-old woman was admitted with a large mass derived from the muscularis propria of the esophagus and the cardia. Submucosal tunneling endoscopic resection was performed. The size of the specimen was 10 × 10 cm, and the postoperative pathology was leiomyoma with red degeneration. After the tumor was removed, a huge tunnel cavity was left. We used metal clips to clamp the tunnel entrance ([Video 1]).